Viral vector vaccines represent one of the most rapidly growing areas in vaccine development. Many vaccines in clinical development for major global infectious diseases, HIV, tuberculosis and malaria, are based on viral vectors. Viral vector vaccines for animals are already on the market, e.g. avipox vector vaccines for companion animals and poultry, avian herpes viruses vectored vaccines for poultry, and vaccinia virus vectored vaccines for wildlife. But other livestock vector vaccines are in development. The advantage of viral vector vaccines is that they can be administered safely due to the use of a vector backbone which is strongly attenuated and does not cause disease in the animal itself. The disadvantage of currently used viral vectors is the existence of maternally derived or antibodies acquired due to a past infection. These antibodies will neutralize the vector virus and thus diminish the success of the vector vaccine. One major impetus for the development of vector vaccines was the occurrence of highly pathogenic influenza virus H5N1 occurring first in Asia and later in Europe and Africa. Several vector vaccine candidates have been developed including fowl poxvirus (Taylor et al, 1988), vaccinia virus (Chambers et al., 1988), Rous sarcoma virus (Hunt et al, 1988), adenoviruses (Tang et al., 2002, Gao et al, 2006), Venezuelan equine encephalitis virus (Schultz-Cherry et al, 2000), Newcastle disease virus (U.S. Pat. No. 6,719,979, Veits et al., 2006, Swayne et al, 2002, Park et al, 2006), herpesvirus of infectious laryngotracheitis (Veits et al. 2003), herpesvirus of turkey (Darteil et al., 1995), and adenovirus based vector vaccines (Hoelscher et al, 2008, Toro et al, 2007). The efficacy of these vector vaccines have been tested in naive birds, but so far no reports have been published on the efficacy of these vector vaccines in birds with a preexisting immunity to the viral vector and/or to the protein coded by the insert.
The virus family Paramyxoviridae includes both human (measles, mumps, parainfluenza and respiratory syncytial virus) and animal pathogens (Newcastle disease virus and rinderpest virus) that cause significant impact on public health as well as the global economy (Lamb et al., 2007). Members of this virus family are defined by having a monopartite, negative sense, single-stranded RNA genome. The Paramyxoviridae family consists of two subfamilies namely Paramyxovirinae and Pneumovirinae. Owing to recent reclassification, the subfamily Paramyxovirinae includes five genera, i.e Morbillivirus, Henipavirus, Rubulavirus, Respirovirus and Avulavirus while Pneumovirinae includes Pneumovirus and Metapneumovirus (Mayo, 2002). Avian paramyxoviruses (APMV) are classified in the genus Avulavirus and comprise nine antigenically distinct serotypes that have been defined using hemagglutination inhibition (HI) tests (Alexander, 1988). Of the nine serotypes, isolates belonging to the APMV-1 subtype can cause a devastating disease in commercial poultry and are classified as velogenic Newcastle disease virus (NDV). Milder forms of NDV are designated as mesogenic and lentogenic isolates, wherein the latter form is mostly asymptomatic in domestic poultry. Isolates belonging to the APMV-2, 3, 6 and 7 have also been associated with disease in domestic poultry. Specifically, infections by isolates of APMV-2 and 3 can cause mild respiratory disease and problems in egg quality and quantity (Bankowski et al., 1981; Redmann et al., 1991; Tumova et al., 1979; Zhang et al., 2007). Isolates of APMV-6 and 7 have been known to infect turkeys, ducks and migratory birds and can induce respiratory disease that may be complicated by secondary infection (Saif et al., 1997; Shortridge et al., 1980). On the other hand, isolates of APMV-4, 5, 8 and 9 have been isolated from ducks, waterfowl and other wild birds but the birds rarely show clinical signs after viral infection (Alexander et al., 1983; Capua et al., 2004; Gough et al., 1984; Maldonado et al., 1995; Shortridge et al., 1980).
The complete genomic sequences of several NDV isolates have been established and used to elucidate the various determinants of NDV virulence (de Leeuw et al., 1999; Krishnamurthy et al., 1998; Zou et al., 2005). In the recent two years several APMV sequences other than APMV1 have been published, such as GenBank accession number EU338414 for APMV-2, EU403085 for APMV-3, FJ177514 for APMV-4, EU622637 for APMV-6, FJ231524 for APMV-7, FJ215863, FJ215864 and FJ619036 for APMV-8, EU910942 for APMV-9. Besides the sequence information, not much is known about virulence factors. Isolates of APMV 2-9 have been mostly isolated from migratory birds. Interestingly, there are very few reports of experimental infection of chickens with such isolates (Saif et al., 1997). Since these APMV circulate widely in wild birds and in certain cases have been isolated from commercial flocks (Zhang et al., 2007) that sometimes cause disease in them (Saif et al., 1997; Shihmanter et al., 1998; Shihmanter et al., 1998), knowledge about their virulence in poultry is needed.
Most of the APMV isolates cause a relatively mild disease that may be exacerbated in the presence of concomitant bacterial or viral infections which might lead to economic impact. In particular, APMV-2 was first isolated as a secondary pathogen in 1956 from chickens affected by acute laryngotracheitis in Southern California (Bankowski et al., 1960). Since then numerous strains of this serotype have been isolated from several avian species signifying that APMV-2 is widely disseminated worldwide (Andral et al., 1984; Bradshaw et al., 1979; Fleury et al., 1979; Goodman et al., 1988; Lang et al., 1975; Lipkind et al., 1982; Lipkind et al., 1979; Zhang et al., 2006). Bankowski et. al. reported that natural as well as artificial exposure of laying turkey hens to APMV-2 caused a pronounced decline in hatchability and poultry yield (Bankowski et al., 1981). Initial examples of APMV-4 isolation were from hunter-killed feral ducks on the Mississippi flyway in the United States (Webster et al., 1976) and from chickens, ducks and geese in Hong Kong during influenza surveillance programs of poultry (Alexander et al., 1979). Apart from an isolate from a ringed teal suffering from hemorrhagic enteritis (Gough et al., 1984), all other isolates were seemingly non-pathogenic in poultry and found to have wide distribution among waterfowl throughout the world (Stanislawek et al., 2002; Tumova et al., 1989; Yamane et al., 1982). Gough et al. reported that no clinical signs and very low HI titers (1:8 or less) were obtained after the intranasal inoculation of one-week old ducklings and two-week old chickens with the isolate from a ringed teal (Gough et al., 1984). Similarly, the first isolates of APMV-6 were also from domestic poultry in Hong Kong as a result of an influenza surveillance program and were reported to be non-pathogenic in chickens based on low HI titers from experimentally infected chickens (Shortridge et al., 1980). However, there have been reports of APMV-6 infection of turkeys leading to mild respiratory disease and egg production problems (Alexander, 2003).
APMV-8 (Goose/Delaware/1053/76) was first isolated in the USA from a hunter-killed Canada goose (Branta canadensis) (Rosenberger et al., 1974). A serological survey (from 1990 to 1992) of wildfowl in southern Spain showed a notable prevalence of APMV-8 antibodies in up to 43% of the tested sera (Maldonado et al., 1995). Another serological study to determine the status of live, healthy mallard ducks in New Zealand for APMV infection revealed the presence of APMV-8 antibodies in 56% of the tested sera (Stanislawek et al., 2002). Warke et al (2008) described that between 16% to 31% of investigated chicken sera might have had APMV-8 antibodies. But due to existing high titers against APMV 1 the probability of a false positive HI test is possible since the sera do not react very specifically in the HI assay. With the exception of a few waterfowl isolates of APMV-8 isolated while the populations were being surveyed for avian influenza viruses (Stallknecht et al., 1991), there has been a dearth of information about the prevalence and pathogenicity of this virus.
The development of reverse genetics systems for the negative stranded RNA genome of NDV has made it possible to insert foreign gene sequences into the genome, thus making it possible to create recombinant NDV vectors for vaccination and gene therapy (Krishnamurthy et al., 2000; Peeters et al., 1999; Roemer-Oberdoerfer et al., 1999). Recombinant NDV vectors expressing foreign viral proteins such as the HA protein of the HI subtype of influenza A virus (Nakaya et al., 2001), VP2 protein of infectious bursal disease virus (IBDV) (Huang et al., 2004), avian influenza virus hemagglutinin of subtype H5 (Veits et al., 2006; Ge et al., 2007) and subtype H7 (Park et al., 2006) have been reported. However the efficacy of most of such vaccines has been demonstrated only in SPF birds. NDV causes a devastating disease in poultry leading to serious economic losses in the poultry industry. Commercial chickens therefore are routinely vaccinated against NDV in most countries of the world. Due to this, chickens from immunized parent flocks have a high level of maternally derived antibodies. Conventional live NDV vaccines provide protection even in the presence of these antibodies. However recombinant NDV vaccines (with foreign gene insertions) are generally more attenuated as compared to live NDV vaccines and their efficacy may be impaired in presence of NDV maternal antibodies. Therefore, there is a need for a vector vaccine platform which can provide the basis for safe vaccines for the expression of heterologous antigens. Ideally, the recombinant vaccine can induce a strong humoral immune response, can be applicable by mass administration, and is inexpensive.